(Jurnal Plastik Rekonstruksi, 2020; Vol 7, No 1, 18-29) BURNS

REVIEW ARTICLE

ANTIOXIDANTS REDUCE TISSUE NECROSIS IN THE ZONE OF

STASIS: REVIEW OF BURN WOUND CONVERSION

Aditya Wardhana1, & Jessica Halim2

1.Burns Section, Division of Plastic Surgery, Dr. Ciptomangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia,
Jakarta, Indonesia
2.Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

ABSTRACT

Summary: Severe burns are devastating condition identified by loss of hemodynamic stability and intravascular
volume. Adequate fluid replacement, nutritional support, and immediate wound grafting can reduce the risk of
infection and mortality. Oxidative stress was shown to have significant role in the burn wound conversion, which
happens when the zone of stasis can’t be salvaged and progresses to necrosis. Decreasing the level of oxidative
stress early may be fundamental in reducing burn injury progression into deeper tissue. Several animal studies
have demonstrated the advance of antioxidant supplementation for burns outcomes. Approach to this salvageable
burn tissue is a breakthrough for new directions in burn management. Antioxidant supplementations was proven
to prevent burn conversion on the ischemic zone. Administering antioxidant post-burn is linked with less
progression of burn depth and inflammatory cytokine release, which alleviates burn-related morbidity and
mortality and improves patient’s quality of life. To date, no clinical trials have been done to reproduce similar
outcomes of this ROS-scavenging therapy as successfully observed in murine models. Antioxidant
supplementation is a promising treatment avenue to halt burn wound conversion following severe burns.
Keywords: Burn wound, wound conversion, burn management, antioxidant

Ringkasan: Kasus luka bakar berat ditandai dengan hilangnya stabilitas hemodinamik dan volume intravaskular.
Pemberian resusitasi yang memadai, asupan nutrisi, dan grafting luka yang tepat dapat mengurangi risiko infeksi
dan angka kematian. Stres oksidatif terbukti memegang peranan penting dalam mempercepat konversi luka bakar,
yang terjadi ketika zona stasis tidak dapat diselamatkan dan berkembang menjadi area nekrosis. Mengurangi level
stres oksidatif penting terbukti mencegah perluasan luka bakar ke jaringan yang lebih dalam. Beberapa penelitian
pada hewan coba menunjukkan efek positif suplementasi antioksidan pada luaran pasien dengan luka bakar.
Terapi yang tertuju pada jaringan luka bakar pada zona statis merupakan terobosan dalam manajemen luka bakar.
Suplemen antioksidan terbukti mencegah konversi luka bakar di zona iskemik. Pemberian antioksidan pasca-luka
bakar mencegah progresi kedalaman luka bakar dan supresi pelepasan sitokin inflamasi, yang dapat mengurangi
tingkat morbiditas dan mortalitas pasca-luka bakar dan meningkatkan kualitas hidup pasien. Sampai saat ini,
belum ada uji klinis yang berhasil membuktikan efek suplementasi antioksidan pada konversi luka bakar seperti
yang telah diamati pada uji hewan coba. Suplementasi antioksidan merupakan pilihan terapi ajuvan yang
menjanjikan untuk supresi konversi luka bakar pada kasus luka bakar berat.
Kata kunci: Luka bakar, konversi luka, managemen luka bakar, antioksidan

Conflicts of Interest Statement:

The author(s) listed in this manuscript declare the absence of any conflict of interest on the subject matter or materials discussed.

Received: 31 03 2020, Revised: 25 04 2020, Accepted: 05 05 2020

Copyright by Halim J, Wardhana A, 2020. │ P-ISSN 2089-6492; E-ISSN 2089-9734 │ DOI: 10.14228/jpr.v7i1.292
Published by Lingkar Studi Bedah Plastik Foundation. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial-No Derivatives
License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without
permission from the journal. This Article can be viewed at www.jprjournal.com

18
 Antioxidants Reduce Tissue Necrosis in The Zone of Stasis
INTRODUCTION
Burns are major health problems causing
fatal complications such as infection and even
death. Severe burn cases are devastating
conditions identified by loss of hemodynamic
stability and intravascular volume requiring
immediate fluid resuscitation followed by
infection control, nutritional support and full
wound coverage and grafting.1 The extent of burn
size and depth is positively correlated with
length of hospital stay, sepsis, mortality, and the
occurrence of burn wound conversion.2
Progression of burn wound depth is a poorly
understood process when the partial-thickness
wounds undergo necrosis and advance into deep
full-thickness burns.3 The eventual depth of the
burn wound necrosis following burn injury is not
readily apparent. This progressive microvascular
deterioration is responsible for increased
morbidity and mortality and greatly affect
treatment outcome in burn patients.4 Over the
last decade, a lot of studies have researched about
preventing burn wound deepening by
reevaluating the effects of fluid resuscitation,
inflammation and infection control, nutritional
requirement, surgical and wound dressing
methods, as well as some novel therapeutic
approach including the effects of antioxidants
supplementation on burn wound conversion.5
This article aims to deliver an up-to-date
summary of the advances in managing burn
wound conversion and investigate the promising
antioxidant supplementation as a new treatment
modality for burn management in the near
future.
EVOLUTION OF BURN INJURY
Burn is a complex and dynamic process
resulting in a myriad of cellular and metabolic
alterations, which alters whole-body responses
long after the burn itself.6 It is categorized into
three main groups based on the causes of injury:
chemical burns caused by strong acids or alkali;
thermal burns caused by fire, hot water, or hot oil;
and electrical burns caused by exposure to high
voltage current or lightning. Extensive research
in burn field has made the intricate and complex
cellular pathophysiology of burn becomes
clearer.
The classic concept of burn proposed by
Jackson burn model categorized burns into three
zones of injury: coagulation zone, static zone, and
hyperemia zone.7 The coagulation zone is the
Copyright by Halim J, Wardhana A, (2020)
P-ISSN 2089-6492; E-ISSN 2089-9734 │ DOI: 10.14228/jpr.v7i1.292
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19
Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
core and the other two zones encircle this necrotic
part of burn injury. The zone of stasis is a
transitional area of active inflammatory process
with reduced vascularization and oxygenation.
The outermost area is the hyperemic zone, where
the vascularization is not impaired. The stasis
zone is the most dynamic and highly dependent
on early resuscitation because this area
progresses to necrosis within 48 hours post-
thermal injury if left inadequately treated. This
may result in a deeper and wider area of injury
within the first 3 days, named burn wound
conversion, which may put the patients in greater
danger.7 The zone of stasis is divided into (a) the
upper subpart with necrotic endothelial cells and
viable adnexal and interstitial cells, which
eventually progresses to full necrosis due to
ischemia, and (b) the lower zones with initially
viable endothelial cells that may progress to
necrosis. Hirth et al. observed that these initially
viable cells 1-hour post-burn was predictive of
tissue necrosis and apoptosis at 24 hours,
contributing to dermal ischemia that rapidly
converts the partial-thickness burns into full-
thickness wounds. Instead of the heat, released
soluble factors (inflammatory cells and cytokines)
are responsible for immediate necrosis and
apoptosis, serving as the leading factor for
wound progression.8
Burns cause extensive tissue destruction and
initiate massive inflammatory reactions leading
to local and distant multiorgan alterations.
Systemic response following thermal injury is
classified into early hypometabolic ‘ebb phase’
happening within the first 48 hours and
hypermetabolic ‘flow’ phase, which starts after 48
hours.9 Reduced oxygenation due to inhalation
injury as well as decreased cardiac output and
peripheral blood flow are the characteristics of
the ebb phase.9 The complex interplay of direct
heat on microcirculation and the chemical
mediators activated following burns are
responsible for the systemic inflammatory
cascades, endothelial dysfunction, and excessive
capillary leakage. Total body surface area (TBSA)
exceeding 20% increases systemic vascular
permeability, resulting in loss of intravascular
fluid to interstitial space, creating generalized
edema and impaired tissue perfusion.1 Greater
burn depth is associated with higher level of
circulating cytokines, which may delay wound
healing, re-epithelization, and promote systemic
infection.6 Intense loss of plasma may lead to
burn shock, thus early repletion of intravascular
volume remains the mainstay of burn
management within the first 24 hours to
 Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
immediately preserve tissue vascularization and
minimize the detrimental effects of inflammatory
responses. At the same time, the release of
catecholamines, antidiuretic hormone,
hemoconcentration may increase pulmonary and
systemic vascular resistance.4
The hypermetabolic-hyperdynamic ‘flow
phase’ occurs 48-72 hours post-burn. It is
characterized by increased oxygen consumption,
increased carbon dioxide production, and
decreased vascular resistance. The body tries to
compensate by increasing cardiac output,
enhances blood flow to distant organs, and
reabsorbing the edema fluid; leaving the body in
a state of hypervolemia, which may cause
pulmonary edema and respiratory distress.
Release of catabolic hormones and insulin
resistance secondary to thermal insults increases
protein turnover, gluconeogenesis, and
production of urea to compensate massive
catabolic processes, which leads to protein
denaturation and muscle wasting contributing to
burn-induced tissue injury. These metabolic
alterations following severe burns may persist up
to 2 years and might interfere with wound
recovery. Harris-Benedict equation predicted
metabolic rates of 110-120% resting energy
expenditure up to 2 years post burn.10
HYPERMETABOLISM INCREASES
BODY STRESS RESPONSE
Burn wounds are characterized by
inadequate tissue perfusion, leading to a state of
ischemia and tissue hypoxia. The hypermetabolic
state induces major stress response and is
associated with myriad biochemical alterations at
molecular levels. As the body tries to respond to
excessive stress, there are 10- to 20-fold increase
in plasma catecholamines level as well as
glucocorticoids and adrenocorticotropic
hormone (ACTH).3, 4 These catabolic hormones
cause inhibition of glycogenesis and rapid-onset
insulin resistance, which establish a state of
elevated proteolysis, gluconeogenesis, energy
consumption, and increased lipid oxidation
causing high levels of circulating plasma free
fatty acid (FFA).4 Moreover, thermal burns
remarkably decreases total antioxidant at cellular
and systemic level early post-burn, and produces
free radicals that overwhelm the scavenging
capacity of the natural oxidative blocking
mechanism.11
Copyright by Halim J, Wardhana A, (2020)
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Halim, Wardhana (2020)
Free radicals and lipid peroxidation are
responsible for systemic inflammatory response
syndrome (SIRS) and organ damage in burn
injury.11 Nuclear factor kappa-B (NF-kB) is
immediately activated following severe burns,
which then initiates a cascade of pro-
inflammatory mediators by macrophages
altogether with sequestered leukocytes.12
Prolonged hypermetabolism in early thermal
injury also increases the production of
inflammatory cytokines such as tumor necrosis
factor-alpha (TNF-a), IL-6, prostaglandin E2, and
induces formation of reactive oxygen species
(ROS), such as superoxide anion, hydroxyl
peroxide, and reactive nitrogen species (RNS),
such as nitric oxide and peroxynitrite.7 The
increased inflammatory mediators in the first few
hours of burn injury, especially IL-6, is
proportionate to the size of burn area, showing
that severe burns is correlated with more
pronounced systemic pro-inflammatory
activities.12 Furthermore, pro-apoptotic factors,
such as Bax, Bcl-Xl, and caspase-3 are
upregulated, causing significant systemic
apoptosis.
Excessive ROS production following burn
injury is harmful to lipids, proteins, and nucleic
acids, which overwhelm endogenous cellular
metabolism and the balance between the
production of free radicals and detoxifications.11
Overproduction of ROS and impaired
antioxidant mechanisms are closely linked to
SIRS, immunosuppression, sepsis and
pulmonary infection, free radical-mediated tissue
damage, and multi-organ failure.7 Abundant
oxidative stress may compromise the immune
system, causing a state of immune suppression
and delayed wound healing.2 This condition
makes burn patients more vulnerable to
secondary infection risking higher mortality rate.
COMBATING BURN WOUND
COMPLICATION
Existing burn management emphasizes on
prevention of complication, promotion of
healing, and treatment for the complications.
Early identification of possibly arising
complications is the key to better burn outcomes.
The massive inflammatory storm following burns
is correlated with a higher incidence of infections,
sepsis, organ failure, and mortality.13 Researchers
have longed for sensitive biomarkers with the
ability to detect and measure life-threatening
20
 Antioxidants Reduce Tissue Necrosis in The Zone of Stasis
adverse events, which will greatly advance the
burn care and reduce post-burn morbidity and
mortality rate. Despite the extensive
understanding of burn pathophysiology, there is
still no reliable biomarkers that can monitor and
predict burn complications.
Burn injury greater than 20% TBSA
necessitates immediate fluid resuscitation to
abate the possible risk of hypovolemic shock due
to massive intravascular volume loss.
Appropriate fluid replacement within 2 hours
post-burn will ensure adequate organ perfusion,
minimize the dysregulated cellular and hormonal
responses, reduce mortality rate, and improves
overall prognosis.13 The widely used Parkland
equation (4 mL/kg/%TBSA of Ringer Lactate
solution) is a simple formula to optimize fluid
delivery by preventing deleterious effects of
over-resuscitation: pulmonary edema, graft
failure, prolonged mechanical ventilation, or
compartment syndrome.14 In contrary, under-
resuscitation may also lead to life-threatening
conditions such as acute kidney injury, wound
conversion, sepsis, multiple organ failure, and
mortality.15
There are two opinions regarding fluid
administration in burn patients. Over-
resuscitation theory, known as the “fluid creep”
or “hyperdynamic resuscitation”, believes that
additional fluid more than the estimated
Parkland formula is associated with improved
survival, less incidence of target-organ damage,
shorter hospital stay and ventilator days, and
lower mortality rate.15 On the other hand, Arlati
et al. demonstrated that permissive hypovolemia
protocol allowed sufficient multi-organ perfusion
and effectively reduced multi-organ
dysfunction.16 Older work from Lund and
colleagues stated similar result where low
volume resuscitation during early post-burn
period significantly reduced the incidence of
acute renal failure and burn-related edema.17
Nonetheless, the classic Parkland formula is still
adapted until further studies could specify the
optimal formula for resuscitation goals.
Ideally, burn patients receive 150% of
recommended fluid based on TBSA calculation.
However, adjustments are made based on
compelling conditions such as the extent of TBSA
estimates, presence of inhalation injury, electrical
burns, and delayed resuscitation. Hemodynamic
parameters such as urine output 0.5 to 1
ml/kg/hour and mean arterial pressure (MAP)
should be regularly checked to monitor
physiologic manipulation in burn patients.13
Copyright by Copyright by Halim J, Wardhana A, (2020)
P-ISSN 2089-6492; E-ISSN 2089-9734 │ DOI: 10.14228/jpr.v7i1.292
This work is licensed under a Creative Commons License Attribution-Noncommercial No Derivative 4.0
21
Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
Maintaining fluid balance during aggressive
fluid administration is challenging without
increasing the risk of fluid accumulation in
interstitial place. Therefore, other parameters for
monitoring fluid balance were popularized to
prevent over-resuscitation; such as intrathoracic
blood volume (ITBV), transpulmonary
thermodilution (TPTD), and extravascular lung
water (EVLW) methods.18
Sepsis is another important cause of burn-
related deaths. However, its timely recognition
remains a challenge. Several biomarkers have
been evaluated for their clinical utility in
diagnosing septicemia. TNF-a, C-Reactive
Protein (CRP), IL-6, IL-4, macrophage colony-
stimulating factor, procalcitonin (PCT), and
erythrocyte sedimentation rate (ESR) were
associated in the development of sepsis.13 IL-8
expression was found to be significantly elevated
following burns, and positively correlated with
increased multiorgan failure, sepsis, and
mortality.19 The use of routine corticosteroid and
immune-enhancing dietary supplements to
suppress inflammation in sepsis also remain
controversial in burn patients.20 However, low
dose hydrocortisone was shown to reduce the
duration of vasopressor administration in burns
with severe shock.21
MEDICAL NUTRITION THERAPY IN
BURN MANAGEMENT
The outcome of burns depends on the time
of treatment. Burn patients experience twice-
normal whole-body metabolic rates, excessive
protein catabolism, loss of protein and
micronutrients through burn exudates, reduced
lean body mass, and state of hyperglycemia.10
These responses are associated with several
adverse events within 48 hours post-burn, such as
severe cachexia, bacteremia, immune
dysfunction, sepsis, and organ failure.13 Severe
burn condition is correlated with decreased
dietary intake due to trauma and possible
orofacial injury, resulting in nutrient deficiency
and malnutrition.22 Tight glycemic control with
adequate dose of insulin was associated with
higher survival rate, considering that insulin also
provides additional immunomodulatory effects,
protects the mucosal and skin barriers, and limits
bacterial translocation.13
Medical nutrition therapy should be the
cornerstone of burn management, considering
that hypermetabolism in burn patients will result
 Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
in cascades of dreadful events, including weight
loss, muscle wasting, immunosuppression,
growth retardation, impaired wound healing,
susceptibility to infection, multiorgan
dysfunction, and death.10 Aggressive
replacement of essential micronutrients and
macronutrients was proven to benefit the
outcome and minimize complications. The
ultimate goal of proper nutrition therapy is to
provide adequate calorie requirement, prevent
starvation and nutrient deficiencies, maintain
body mass, restore protein loss, and in the end
reduce infection rate and promote faster wound
healing.22
The concept of hyperalimentation is
implemented for nutritional maintenance in
critically ill burn patients. Nutrient requirements
are markedly increased in patients with TBSA
exceeding 20%, prior malnutrition, or pre-
existing diseases such as HIV/AIDS. The
estimated requirement may vary according to
patient’s age, pregnancy status, organ failure, and
presence of infection.23 Total energy requirement
(TER) for burn patients is equal to (1000 kcal x
BSA[m2] + 25 x %TBSA) which is proportioned
into 60-70% glucose. Increased muscle catabolism
requires higher protein intake to aid tissue repair
(recommended proportion of 20% to 25% from
TER). The benefit of additional lipid requirement
is dose-dependent and limited to only 15% of TER
to reduce infectious morbidity and shorten
hospitalization period.23
Nutritional support is better delivered
through enteral route; oral, nasogastric and
nasojejunal feeding, are the routes of choice.
Nutrient intake should be commenced
immediately or at least within 24 to 48 hours
following burns.24 Early nutrition initiation will
blunt the hypermetabolic state and reduce
circulating cortisol, catecholamines, and
glucagon hormones. In-vivo study by Mochizuki
et al. showed that initiation of enteral nutrition 2
hours post-burn significantly reduces
hypermetabolism within 2 weeks than the control
group fed 3 days post-burn, stressing the benefits
of prompt nutrition therapy.25 Excessive stress
response, ischemia, complement activation, ROS,
and release of inflammatory cytokines and
endotoxins also contribute to intestinal barrier
dysfunction.26 Increased intestinal permeability
promotes massive bacterial translocation to
distant organs that eventually leads to sepsis,
immune disturbance, burn shock, multi-organ
dysfunction, and mortality.10 Therefore, early
Copyright by Halim J, Wardhana A, (2020)
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Halim, Wardhana (2020)
enteral nutrition is beneficial to maintain gut
mucosal integrity, motility, and perfusion, which
could prevent subsequent ileus or intestinal
hypoperfusion. Early fluid resuscitation and
nutrition intake should be taken as preventive
approach and personalized for each patient; both
are the backbone of burns management.27
BURN WOUND CONVERSION AS
POOR PREDICTOR OF OUTCOME
Burn wound conversion is the progression
of ischemic partial thickness wound into non-
viable full thickness wound, thus increasing the
portion of third-degree burn. Referring to the
conventional depiction of burn zones by Jackson,
burn progression happens when the zone of
stasis can’t be salvaged and thus progresses to
necrosis. This progression is dangerous because it
often contributes to greater surface area and
depth, increasing the risk of complications and
mortality within 24 hours.28 Burn wound
conversion is predisposed by local and systemic
factors. Infections, tissue desiccation, wound
edema, and eschar contributes locally to progress
burn wound into necrosis. Systemic homeostasis
is also jeopardized following burn injury related
to impaired perfusion, metabolic derangements,
and suboptimal general health status.3
Few studies have investigated several
prognostic factors that may progress or regress
wound conversion in burn injury. It was initially
believed that vasoconstriction compromised
tissue perfusion and contributed to its
advancement into full-thickness burn.3 At the
same time, peripheral vasodilation induced by an
elevated level of inducible nitric oxide synthase
(iNOS) upregulated downstream pathway of
inflammatory mediators and ROS, which
threaten the tissue viability in the stasis and
hyperemia zone.29 The understanding of
pathogenesis of wound conversion has evolved
greatly, from the well-accepted theories of micro
thrombosis, ischemia, and ROS, to the most
recent concept highlighting the role of autophagy
as a potential determinant behind secondary
burn damage.3,8,28,30 Older works revealed that
more apoptotic activity, ischemic cell death, and
tissue death were concentrated in the zone of
stasis.28
Adequate wound debridement, dressings,
cytokine- and inflammatory cascade-targeted
therapy may also reduce the inflammatory
activity in burn wounds. Recent work by Tan and
22
 Antioxidants Reduce Tissue Necrosis in The Zone of Stasis
colleagues reported that the activity of autophagy
and apoptosis in burns occur at different time
points, thus augmenting autophagy with
rapamycin antibiotic could improve wound
healing and lessen burn conversion.30 The current
trend considers that careful approach to this
salvageable burn tissue is a breakthrough for new
directions in burn management. Controlling burn
conversion holds the key to obviate the necessity
for surgery while pursuing limited scarring
during the healing process.11
REVERSING PROGRESSION OF
BURN WOUND DEPTH
Progressive expansion of ischemic area to
non-viable necrotic tissue has been a major focus
of research. Immediate commencement of fluid
replacement minimizes incidences of burn shock,
burn-related kidney injury, life-threatening
electrolyte imbalance, and mortality.15 A rat
model illustrated by Kim et al showed that
adequate resuscitation rate (4 to
8ml/kgBW/%burn) prevents prolonged
ischemia in burn wounds while suboptimal fluid
replacement (<4ml/kgBW/%burn) exacerbates
burn wound deepening. The study also
demonstrated that over-resuscitation of 6-
8ml/kgBW/%burn is correlated with respiratory
distress and tissue edema.31 They proposed that
the benefit of resuscitation is varied according to
the depth of the initial burn wound. Similar result
was reproduced by Carvajal et al, illustrating that
burn resuscitation restores and maintains
maximal perfusion pressure in pediatric patients,
which accelerates spontaneous healing and
minimizes wound progression.32 Despite the
importance of fluid therapy in burn management,
little is known about the ideal type and volume of
fluid, rate of fluid administration, or method of
monitoring. No single formula for optimal
resuscitation was proven to be superior. Hence,
fluid therapy should be carefully administrated
and hourly titrated according to physiological
response and various clinical outcomes.33
Studies on burn conversion were mainly
done in-vivo using the comb burn model to
replicate the zones of burns. The last decade of
research has shown growing interest in other
local and systemic intervention. Targeting
exaggerated inflammatory responses such as
TNF-a, IL-6, IL-4, or complement cascades for
immunomodulation are considered as a novel
approach to halt burn progression. Eski et al.
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23
Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
demonstrated that reduced tissue necrosis was
observed in both short-term (3-day) and long-
term (21-day) follow-up by treating thermal
injury with cerium nitrate baths, which was
renowned to alleviate TNF-a levels, decrease
leukocyte activation, and activate phagocyte
activity.34 Reduced burn conversion was also
successfully demonstrated with systemic or local
transplantation of mesenchymal stem cells
(MSCs) by attenuating burn-induced apoptosis,
downregulating pro-inflammatory cytokines, up-
regulating anti-inflammatory mediators,
relieving oxidative stress, and promoting better
vascularization.35 Early administration of MSCs
(30 minutes post-burn) was considered favorable
to preserve more vital tissue in the zone of stasis,
reaffirming the therapeutic effects of stem cell
treatment in burns.36
A recent study by Singer et al. elucidated
that tadalafil was deemed superior compared to
naproxen and N-acetyl cysteine in reducing
necrosis in the ischemic zone of a rat burn
model.37 Tobalem and colleagues treated burn
wound with erythropoietin (EPO). The anti-
inflammatory, angiogenic, and vasodilatory
properties of this hormone dose- and time-
dependently limited necrosis and burn depth
progression by improving vascular perfusion.38
The authors also suggested that immediate warm
water bath after burns decreased ischemia by
promoting vasodilation, contradicting to the old
belief that hypothermia or cold-water treatment
can limit initial cellular injury, protect post-
traumatic circulation, and downregulate
inflammatory gene expression.39 Guo et al. also
observed the benefit of hydrogen-rich saline on
early burn progression following deep burns.40
Another approach such as hyperbaric oxygen
treatment (HBOT), was investigated for its
instant anti-edematous and anti-hypoxic relief
and has successfully reduced necrosis and
improved wound healing in human burn
models.41
Local wound, care including antibiotics,
dressings, and bioactive agents, are used to
accelerate wound healing and minimize damage
induced by the initial burn injury. Dressings
function to create a moist environment, protect
the wound from environmental insult or
contamination, provide drainage absorption and
pain control.28 Antibiotics are used in addition to
silver sulfadiazine to reduce microbial load and
prevent infection, especially in deeper wounds.
Other mechanisms such as conventional burn
excision and eschar removal have not shown
 Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
consistent ability to prevent necrosis in the stasis
zone, suggesting other more important cascades
responsible in the pathophysiology of wound
conversion.28
ANTIOXIDANT AS BODY DEFENSE
SYSTEM
Thermal injury causes physiological
derangement and alters the body response at
cellular and systemic level. Recalling the
pathophysiology of burn, consequent ischemia
and inflammation post-burn lead to
overwhelming ROS production and insufficient
scavenging system, which are the greatest
contributors for the development of burn
complications. The level of ROS and antioxidants
in the circulation is positively correlated with the
severity of burn area.5 Uncontrolled circulating
oxidative stress level along with plummeted
inflammatory activity are dreadful and correlated
with higher morbidity and mortality rate.42
It is natural that the presence of oxidative
stress is counteracted by equal synthesis of
antioxidants. Antioxidant, considered as the first
line of defense mechanism against free radical
damage, delays, removes, and prevents oxidation
process that may harm target molecules.43 These
scavenger systems are capable of converting the
radicals to less reactive form and neutralizing the
deleterious effect of ROS to the body. A depletion
of antioxidants is correlated with higher disease
occurrence and poorer outcomes.44 Therefore,
dietary antioxidants are essential in restoring
circulating endogenous antioxidants and
suppressing oxidative stress-induced damages.
Numerous studies have highlighted the potential
role of antioxidants in preventing degenerative
diseases-related morbidity and mortality as
shown in cancer, coronary heart disease, obesity,
type 2 diabetes, Alzheimer’s disease,
hypertension, cataract, etc.45, 46
Antioxidants are generated endogenously
or exogenously supplemented in the form of
natural and synthetic antioxidants.43, 44
Endogenous antioxidants can be classified into
enzymatic and non-enzymatic compounds,
which is further categorized into metabolic and
nutrient antioxidants.45 The endogenous
antioxidant enzymes, such as glutathione
peroxidase, catalase, and superoxide dismutase,
are naturally produced in the body to protect
against free radicals-induced cellular damage.45
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P-ISSN 2089-6492; E-ISSN 2089-9734 │ DOI: 10.14228/jpr.v7i1.292
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Halim, Wardhana (2020)
Non-enzymatic metabolic compounds are
byproduct of metabolism such as lipoic acid, L-
arginine, glutathione, coenzyme Q10, uric acid,
bilirubin, etc. Nutrient antioxidants can’t be
produced in the body and thus are supplied
through foods, such as fruits and vegetables
containing vitamin C (ascorbic acid), vitamin E
(tocopherols), vitamin A (carotenoids) and other
phenolic compounds.45,47 The water-soluble
antioxidant acts as ROS neutralizer in aqueous
phase before initiation of lipid peroxidation while
the lipid soluble antioxidant, such as vitamin E,
protects the membrane fatty acids from being
oxidized. Others, such as beta carotene and
carotenoids are believed to protect the lipid-rich
tissue from deleterious effect of free radicals.48
Antioxidants also come in synthetic form, which
is chemically synthesized and fortified to food.
Butylhydroxyanisole, butylhydroxytoluene, and
gallates, are some examples of synthetic
antioxidant. It is important to note that avoiding
external oxidants source such as cigarette,
alcohol, bad food, and stress is as important as
taking antioxidant-rich diet.
ROLE OF ANTIOXIDANTS
SUPPLEMENTATION IN BURN
WOUND CONVERSION
A Deficiency of micronutrients is often
found in critically ill patient, which may benefit
from administration of trace elements such as
antioxidants.49 Antioxidants supplementation for
ill trauma patients; such as burns, sepsis, post-
surgical procedure, cancer, or organ
transplantation, was associated with better
outcome, however its true benefit for routine
treatment still remains controversial.50 Contrary
to the previous statement, some studies implied
that antioxidant supplementations exert no
significant benefit on disease control and in turn
may act as pro-oxidant if consumed significantly
above the recommended dietary intakes.45 A
Cochrane systematic review reported that
administration of antioxidants (beta-carotene,
vitamin E, and higher doses of vitamin A) for
primary or secondary prevention in healthy and
ill patients with various underlying diseases
seem to increase mortality.51
Antioxidants therapy for burn
management has been widely researched at
molecular level for its efficacy in restoring
circulating antioxidant defenses. Massive
decrease in SOD, glutathione, catalase, alpha-
24
 Antioxidants Reduce Tissue Necrosis in The Zone of Stasis
tocopherol, and ascorbic acid have been
documented in burn injury.7 Inhalation injury is
also a contributing factor that accelerates the
reduction in plasma antioxidants. Therapies
targeted to block the xanthine oxidase activity
may alleviate ROS-induce damage by scavenging
ROS from the circulation.22 Thus, antioxidants
along with other trace element supplement have
been approved for their benefits in accelerating
wound healing post-burns, by reducing the risk
of pulmonary infection and length of hospital
stay.5 Understanding the role of ROS in the
pathophysiology of burn has made antioxidant
therapy as a promising step in burns
management.
Numerous studies stated that antioxidant
supplementations for burn patients significantly
promote faster wound healing, shortens hospital
stays, reduce mortality rate, and decrease
incidence of infection in all cases.5 A review by
Adjepong et al. concluded that administration of
trace elements such as vitamin A, C, E, zinc,
selenium, and N-acetylcysteine following burn
dose-dependently increased the level of
circulating antioxidants that was initially scarce
up to a normalized level, which is a good
indicator for faster recovery.22 Vitamin E is used
to scavenge intracellular free radicals while
vitamin C, which is diminished early post-burn,
is for scavenging free radicals extracellularly.52
Early administration of high-dose ascorbic acid
may reduce the needed amount of fluid
resuscitation, resulting in less tissue edema and
more body weight gain.53 Despite the risk of renal
failure following administration of high dose of
vitamin C, studies showed that burn areas greater
than 20% may gain more benefit from this
intervention compared with placebo.52, 54
Despite these outstanding outcomes,
antioxidant supplementation still requires more
exploration through clinical trials, since most of
the publications are small-sized research with
various dosing and outcome parameters. A pilot
study by Raposio et al. evaluated the plasma
oxidative stress in partial thickness burns after 2
weeks of antioxidant supplementation and the
result showed no significant changes in plasma
oxidants level. This finding indicated that the use
of antioxidant supplements for medicinal
products should be sufficiently evaluated.55
Individual trace elements should also be
explored, as Ross et al. and Berger et al. stated
that selenium plays a significant role in immune
function and thus is worth a lone investigation of
its effect on oxidative stress.56
Copyright by Copyright by Halim J, Wardhana A, (2020)
P-ISSN 2089-6492; E-ISSN 2089-9734 │ DOI: 10.14228/jpr.v7i1.292
This work is licensed under a Creative Commons License Attribution-Noncommercial No Derivative 4.0
25
Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
Considering all successful studies about
antioxidant supplementation for burn patients,
however little is known whether this intervention
may have an effect to salvage the stasis zone in
burn. A randomized controlled experiment done
by Singer et al. on rat models described that
administration of curcumin, believed to possess
high antioxidant properties, on day 1, 2, 3 post-
brass comb-induced burn injury, reduced the
burn progression to full-thickness necrosis in the
ischemic area.57 The result showed significant
difference between the treated and placebo
subjects even on the first day at 30% and 63%
respectively (p=0.003). The experiment was
reproducible and consistent which showed less
progression of interspace ischemic area to
necrosis following administration of intravenous
crude and purified curcumin on day 7 after the
burn injury. 58
Other authors have tried out other sources
of antioxidants to minimize free radical damage
and prevent burn wound progression through
extensive animal studies. Using a rat deep-burn
model, Fang et al. also showed that
administration of astaxanthin (strong antioxidant
element) dose-dependently reduced progression
rate in the stasis zone, by suppressing the release
of inflammatory mediators and reducing burn-
induced apoptosis.59 Similar result was observed
in other studies utilizing N-acetylcysteine (NAC)
one hour post-burn and metal chelator disodium
ethylenediaminetetraacetic acid (EDTA)
containing iron and calcium ions.58, 60 Enhancing
the trace elements zinc and allopurinol were also
proven beneficial in combating ROS and
enhancing immune function.22 Topical
application of human recombinant copper-zinc
SOD successfully salvaged the zone of stasis and
promoted better wound healing in burn injury.61
However, many discrepancies of the study result
were found and therefore suggest further
investigation for optimal utilization of these
agents.
SUMMARY
Abundant oxidative stress and circulating
inflammatory cytokines storm following burn
has made the wound susceptible to depth
progression if not managed adequately.
Antioxidant has shown promising standpoints to
slow down and counter the toxic implications of
free radicals, suggesting that maintenance of
adequate antioxidants level is essential in burn
 Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020 Halim, Wardhana (2020)

patients. Administration of dietary antioxidants Injured Patient. Anesthesiology.

and trace elements significantly enhanced rate of
recovery, prevented complications (infection,
sepsis, pneumonia) and reduced mortality rate.5
Antioxidant supplementations were also proven
to prevent burn conversion on the ischemic zone.
Future studies are therefore required to translate
these promising results from animal studies to
real human models. Antioxidant therapy
represents a promising avenue to be adjuvant
therapy in many clinical conditions, especially for
burn management.
Correspondence regarding this article should be
addressed to:
Jessica Halim. Faculty of Medicine, Universitas Indonesia,
Jakarta, 10430, Indoneisa.
E-Mail: jessiica.halim@yahoo.com
REFERENCES
1. Ruiz-Castilla M, Roca O, Masclans JR, Barret
JP. Recent Advances In Biomarkers In Severe
Burns. Shock. 2016;45(2):117-25.
2. Rowan MP, Cancio LC, Elster EA,
Burmeister DM, Rose LF, Natesan S, et al.
Burn wound healing and treatment: review
and advancements. Crit Care. 2015;19:243.
3. Singh V, Devgan L, Bhat S, Milner SM. The
pathogenesis of burn wound conversion.
Ann Plast Surg. 2007;59(1):109-15.
4. Auger C, Samadi O, Jeschke MG. The
biochemical alterations underlying post-
burn hypermetabolism. 2017;1863(10):2633-
44.
5. Al-Jawad F, Sahib A, Al-Kaisy A. Role of
Antioxidants in the Treatment of Burn
Lesions. Ann Burns Fire Disasters.
2008;21(4):186-91.
6. Jeschke MG, Chinkes DL, Finnerty CC, Kulp
G, Suman OE, Norbury WB, et al.
Pathophysiologic response to severe burn
injury. Ann Surg. 2008;248(3):387-401.
7. Nielson CB, Duethman NC, Howard JM,
Moncure M, Wood JG. Burns:
Pathophysiology of Systemic Complications
and Current Management. J Burn Care Res.
2017;38(1):e469-81.
8. Hirth D, McClain SA, Singer AJ, Clark RA.
Endothelial necrosis at 1h post-burn predicts
progression of tissue injury. Wound Repair
Regen. 2013;21(4):563-70.
9. Bittner EA, Shank E, Woodson L, Martyn JJ.
Acute and Perioperative Care of the Burn-
2015;122(2):448-64.
10. Rodriguez NA, Jeschke MG, Williams FN,
Kamolz LP, Herndon DN. Nutrition in
Burns: Galveston Contributions. JPEN J
Parenter Enteral Nutr. 2011;35(6):704-14.
11. Horton JW. Free radicals and lipid
peroxidation mediated injury in burn
trauma: the role of antioxidant therapy.
Toxicology. 2003;189(1-2):75-88.
12. Agay D, Andriollo-Sanchez M, Claeyssen R,
Touvard L, Denis J, Roussel AM, et al.
Interleukin-6, TNF-alpha and interleukin-1
beta levels in blood and tissue in severely
burned rats. Eur Cytokine Netw.
2008;19(1):1-7.
13. Snell JA, Loh NHW, Mahambrey T,
Shokrollahi K. Clinical review: The critical
care management of the burn patient. Crit
Care. 172013. p. 241.
14. Tricklebank S. Modern trends in fluid
therapy for burns. Burns. 2009;35(6):757-67.
15. Chan J, Ghosh S. Fluid Resuscitation in
Burns: An Update:.
https://doiorg/101177/10249079090160011
2. 2017.
16. Arlati S, Storti E, Pradella V, Bucci L, Vitolo
A, Pulici M. Decreased fluid volume to
reduce organ damage: a new approach to
burn shock resuscitation? A preliminary
study. Resuscitation. 2007;72(3):371-8.
17. Lund T. The 1999 Everett Idris Evans
memorial lecture. Edema generation
following thermal injury: an update. J Burn
Care Rehabil. 1999;20(6):445-52.
18. Sánchez M, García-de-Lorenzo A, Herrero E,
Lopez T, Galvan B, Asensio MJ, et al. A
protocol for resuscitation of severe burn
patients guided by transpulmonary
thermodilution and lactate levels: a 3-year
prospective cohort study. Crit Care. 172013.
p. R176.
19. Kraft R, Herndon DN, Finnerty CC, Cox RA,
Song J, Jeschke MG. Predictive Value of IL-8
for Sepsis and Severe Infections after Burn
Injury - A Clinical Study. Shock.
2015;43(3):222-7.
20. Greenhalgh DG. Sepsis in the burn patient: a
different problem than sepsis in the general
population. Burns Trauma. 52017.
21. Venet F, Plassais J, Textoris J, Cazalis MA,
Pachot A, Bertin-Maghit M, et al. Low-dose
hydrocortisone reduces norepinephrine
duration in severe burn patients: a
randomized clinical trial. Crit Care. 192015.

Copyright by Halim J, Wardhana A, (2020)

P-ISSN 2089-6492; E-ISSN 2089-9734 │ DOI: 10.14228/jpr.v7i1.292
This work is licensed under a Creative Commons License Attribution-Noncommercial No Derivative 4.0
26
 Antioxidants Reduce Tissue Necrosis in The Zone of Stasis
22. Adjepong M, Agbenorku P, Brown P, Oduro
I. The role of antioxidant micronutrients in
the rate of recovery of burn patients: a
systematic review. Burns Trauma. 42016.
23. A. Prins RD (SA) M. Nutritional
management of the burn patient.
http://dxdoiorg/101080/160706582009117
34211. 2016.
24. Mandell SP, Gibran NS. Early Enteral
Nutrition for Burn Injury. Adv Wound Care
(New Rochelle). 32014. p. 64-70.
25. Mochizuki H, Trocki O, Dominioni L,
Alexander JW. Reduction of postburn
hypermetabolism by early enteral feeding.
Curr Surg. 1985;42(2):121-5.
26. He W, Wang Y, Wang P, Wang F. Intestinal
barrier dysfunction in severe burn injury.
Burns & Trauma. 2019;7(1):1-11.
27. Natarajan M. Recent Concepts in Nutritional
Therapy in Critically Ill Burn Patients.
International Journal of Nutrition,
Pharmacology, Neurological Diseases.
2019;9(1):4-36.
28. Salibian AA, Del Rosario AT, De Almeida
Moura Severo L, Nguyen L, Banyard DA,
Toranto JD, et al. Current concepts on burn
wound conversion – a review of recent
advances in understanding the secondary
progressions of burns. Burns.
2016;42(5):1025-35.
29. Rawlingson A. Nitric oxide, inflammation
and acute burn injury. Burns. 2003;29(7):631-
40.
30. Tan JQ, Zhang HH, Lei ZJ, Ren P, Deng C, Li
XY, et al. The roles of autophagy and
apoptosis in burn wound progression in
rats. Burns. 2013;39(8):1551-6.
31. Kim DE, Uniformed Services University of
the Health Sciences B, Maryland, Phillips
TM, Uniformed Services University of the
Health Sciences B, Maryland, Jeng JC,
Uniformed Services University of the Health
Sciences B, Maryland, et al. Microvascular
Assessment of Burn Depth Conversion
during Varying Resuscitation Conditions.
The Journal of Burn Care & Rehabilitation.
2019;22(6):406-16.
32. Carvajal HF. Fluid resuscitation of pediatric
burn victims: a critical appraisal. Pediatr
Nephrol. 1994;8(3):357-66.
33. Bacomo FK, Chung KK. A primer on burn
resuscitation. J Emerg Trauma Shock. 42011.
p. 109-13.
34. Eski M, Ozer F, Firat C, Alhan D, Arslan N,
Senturk T, et al. Cerium nitrate treatment
Copyright by Copyright by Halim J, Wardhana A, (2020)
P-ISSN 2089-6492; E-ISSN 2089-9734 │ DOI: 10.14228/jpr.v7i1.292
This work is licensed under a Creative Commons License Attribution-Noncommercial No Derivative 4.0
27
Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
prevents progressive tissue necrosis in the
zone of stasis following burn. Burns.
2012;38(2):283-9.
35. Abbas OL, Ozatik O, Gonen ZB, Ogut S,
Entok E, Ozatik FY, et al. Prevention of Burn
Wound Progression by Mesenchymal Stem
Cell Transplantation: Deeper Insights Into
Underlying Mechanisms. Ann Plast Surg.
2018;81(6):715-24.
36. Oksuz S, Ulkur E, Oncul O, Kose GT,
Kucukodaci Z, Urhan M. The effect of
subcutaneous mesenchymal stem cell
injection on statis zone and apoptosis in an
experimental burn model. Plast Reconstr
Surg. 2013;131(3):463-71.
37. Singer AJ, Towery H, McClain SA. Effect of
tadalafil on reduction of necrosis in the
ischemic zone in a rat comb burn model.:
Epub; 2019 [
38. Tobalem M, Harder Y, Schuster T, Rezaeian
F, Wettstein R. Erythropoietin in the
prevention of experimental burn
progression. Br J Surg. 2012;99(9):1295-303.
39. Schaser KD, Stover JF, Melcher I, Lauffer A,
Haas NP, Bail HJ, et al. Local cooling restores
microcirculatory hemodynamics after closed
soft-tissue trauma in rats. J Trauma.
2006;61(3):642-9.
40. Guo SX, Jin YY, Fang Q, You CG, Wang XG,
Hu XL, et al. Beneficial Effects of Hydrogen-
Rich Saline on Early Burn-Wound
Progression in Rats. PLoS One. 102015.
41. Turkaslan T, Yogun N, Cimsit M, Solakoglu
S, Ozdemir C, Ozsoy Z. Is HBOT treatment
effective in recovering zone of stasis? An
experimental immunohistochemical study.
Burns. 2010;36(4):539-44.
42. Trifunovic A, Wredenberg A, Falkenberg M,
Spelbrink JN, Rovio AT, Bruder CE, et al.
Premature ageing in mice expressing
defective mitochondrial DNA polymerase.
Nature. 2004;429(6990):417-23.
43. Yadav A. (PDF) Antioxidants and its
functions in human body - A Review. 2019.
44. Liu Z, Ren Z, Zhang J, Chuang C-C,
Kandaswamy E, Zhou T, et al. Role of ROS
and Nutritional Antioxidants in Human
Diseases Frontiers Physiology.
2018;17(9):477.
45. Pham-Huy LA, He H, Pham-Huy C. Free
Radicals, Antioxidants in Disease and
Health. Int J Biomed Sci. 42008. p. 89-96.
46. Willcox JK, Ash SL, Catignani GL.
Antioxidants and prevention of chronic
 Jurnal Plastik Rekonstruksi, Vol. 7, No. 1, 2020
disease. Crit Rev Food Sci Nutr.
2004;44(4):275-95.
47. Liguori I, Russo G, Curcio F, Bulli G, Aran L,
Della-Morte D, et al. Oxidative stress, aging,
and diseases. Clin Interv Aging. 132018. p.
757-72.
48. Reddy P, Jialal I. Biochemistry, Vitamin, Fat
Soluble. 2018.
49. Berger MM, Oudemans-van Straaten HM.
Vitamin C supplementation in the critically
ill patient. Curr Opin Clin Nutr Metab Care.
2015;18(2):193-201.
50. Parker R, Rice MJ. Benefits of antioxidant
supplementation in multi-trauma patients.
Romanian Journal of Anaesthesia and
Intensive Care. 2015;22:77-8.
51. Bjelakovic G, Nikolova D, Gluud LL,
SImonetti RG, Gluud C. Antioxidant
supplements for prevention of mortality in
healthy participants and patients with
various diseases. Cochrane Database of
Systematic Reviews. 2012.
52. Sahib A, Al-Jawad F, Alkaisy A. Effect of
Antioxidants on the Incidence of Wound
Infection in Burn Patients. Ann Burns Fire
Disasters. 2010;23(4):199-205.
53. Rizzo JA, Rowan MP, Driscoll IR, Chung KK,
Friedman BC. Vitamin C in Burn
Resuscitation. Crit Care Clin. 2016;32(4):539-
46.
54. Kahn SA, Beers RJ, Lentz CW. Resuscitation
after severe burn injury using high-dose
ascorbic acid: a retrospective review. J Burn
Care Res. 2011;32(1):110-7.
55. Raposio E, Grieco MP, Caleffi E. Evaluation
of plasma oxidative stress, with or without
antioxidant supplementation, in superficial
partial thickness burn patients: a pilot study.
J Plast Surg Hand Surg. 2017;51(6):393-8.
56. Ziegler R, Emory University ACR,
Pennsylvania State U, Benjamin HC,
Bloomberg School of Public H,
caballero@jhu.edu, et al. Modern nutrition in
health and disease: Eleventh edition. 2019.
57. Singer AJ, McClain SA, Romanov A, Rooney
J, Zimmerman T. Curcumin reduces burn
progression in rats. Acad Emerg Med.
2007;14(12):1125-9.
58. Singer AJ, Taira BR, Lin F, Lim T, Anderson
R, McClain SA, et al. Curcumin reduces
injury progression in a rat comb burn model.
J Burn Care Res. 2011;32(1):135-42.
59. Fang Q, Guo S, Zhou H, Han R, Wu P, Han
C. Astaxanthin protects against early burn-
wound progression in rats by attenuating
Copyright by Halim J, Wardhana A, (2020)
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This work is licensed under a Creative Commons License Attribution-Noncommercial No Derivative 4.0
Halim, Wardhana (2020)
oxidative stress-induced inflammation and
mitochondria-related apoptosis. Sci Rep.
2017;7:41440.
60. Wang CZ, Ayadi AE, Goswamy J, Finnerty
CC, Mifflin R, Sousse L, et al. Topically
applied metal chelator reduces thermal
injury progression in a rat model of brass
comb burn. Burns. 2015;41(8):1775-87.
61. Shalom A, Kramer E, Westreich M.
Protective effect of human recombinant
copper-zinc superoxide dismutase on zone
of stasis survival in burns in rats. Ann Plast
Surg. 2011;66(6):607-9.
LIST OF ABBREVIATIONS
ACTH - AdrenoCorticoTropic Hormone
CRP - C-Reactive Protein
EDTA - EthyleneDiamineTetraacetic Acid
EPO – Erythropoietin
ESR - Erythrocyte Sedimentation Rate
EVLW - ExtraVascular Lung Water
HBOT - Hyperbaric Oxygen Treatment
IL – InterLeukin
iNOS - inducible Nitric Oxide Synthase
ITBV - Intrathoracic Blood Volume
MAP - Mean Arterial Pressure
MSC - Mesenchymal Stem Cells
NAC - N-Acetylcystein
NF-kB - Nuclear Factor Kappa B Cells
RNS - Reactive Nitrogen Species
ROS - Reactive Oxygen Species
SOD - SuperOxide Dismutase
TBSA - Total Burn Surface Area
TER - Total Energy Requirement
TNF - Tumor Necrosis Factor
TPTD - TransPulmonary ThermoDilution
28